Charcot-Marie-Tooth Disease, Type Ia

Poster presentation highlights SMART adenine base editors (ABEs)small enough to be packaged into a single adeno-associated virus (AAV) Data demonstrate compact SMART system optimizations allowing fortherapeutically-relevant genome editing EMERYVILLE, Calif., Oct. 14, 2024 (GLOBE NEWSWIRE) -- Metagenomi, Inc. (Nasdaq: MGX), a precision genetic medicines company committed to developing curative therapeutics for patients using its proprietary gene editing toolbox, today presented a poster titled “Engineering of compact and efficient adenine base editors from metagenomic derived systems” at the American Institute of Chemical Engineers (AIChE) 7th International Conference on CRISPR Technologies in San Diego, CA. “We are thrilled to share the progress we’ve made with our compact SMART systems,” said Chris Brown, PhD and Head of Discovery at Metagenomi. “Our update highlights the improved efficiency of our SMART platform across multiple targets and cell types. We demonstrated that our SMART nucleases can be engineered into functional base editors within the packaging limits of standard AAV. We believe the improved editing efficiency of these SMART systems will enable pursuit of neuromuscular targets, either on our own or in partnerships.” Metagenomi’s SMART platform potentially addresses a key challenge of in vivo gene editing: efficient delivery of gene editing components to tissues beyond the liver. Currently, AAV is an established approach for delivery to extrahepatic tissues, which is necessary for treating neuromuscular diseases such as Duchenne muscular dystrophy (DMD), familial amyotrophic lateral sclerosis (ALS), and Charcot-Marie-Tooth disease type 1A (CMT1A). Traditional gene editing tools such as SpCas9 exceed the cargo capacity of standard AAV vectors, potentially necessitating the need for dual AAV systems, which may reduce overall editing efficiency, increase required dosages, and complicate the manufacturing process. Metagenomi’s SMART genome editing systems are small enough to be packaged into standard AAV vectors, even when additional effector domains are included for base editing, potentially enabling a differentiated therapeutic approach. Metagenomi has taken a multi-pronged approach to optimizing the SMART platform since its initial discovery (Aliaga Goltsman, Daniela S., et al. “Compact...” Nature Communications, vol. 13, no. 1), including structure-guided engineering enabled through collaboration with Professor David Taylor and his lab at UT Austin (Ocampo, Rodrigo Fregoso, et al. "DNA..." bioRxiv). In addition, Metagenomi has applied advanced artificial intelligence (AI) tools trained on natural SMART enzymes, which was presented at the Cold Spring Harbor Laboratory (CSHL) CRISPR Frontiers conference earlier this year. The AI-driven approach underscores the importance of leveraging multiple cutting-edge techniques to advance next-generation gene editing systems. About MetagenomiMetagenomi is a precision genetic medicines company committed to developing curative therapeutics for patients using its proprietary, comprehensive metagenomics-derived toolbox. Metagenomi is harnessing the power of metagenomics, the study of genetic material recovered from the natural environment, to unlock four billion years of microbial evolution to discover and develop a suite of novel editing tools capable of correcting any type of genetic mutation found anywhere in the genome. Its comprehensive genome editing toolbox includes programmable nucleases, base editors, and RNA and DNA-mediated integration systems (including prime editing systems and clustered regularly interspaced short palindromic repeat associated transposases). Metagenomi believes its diverse and modular toolbox positions the company to access the entire genome and select the optimal tool to unlock the full potential of genome editing for patients. For more information, please visit https://​metageno​mi​.co. Cautionary Note Regarding Forward‐​Looking StatementsThis press release contains ​“forward-looking statements” within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934, each as amended. Such statements, which are often indicated by terms such as ​“anticipate,” ​“believe,” ​“could,” ​“estimate,” ​“expect,” ​“goal,” ​“intend,” ​“look forward to,” ​“may,” ​“plan,” ​“potential,” ​“predict,” ​“project,” ​“should,” ​“will,” ​“would” and similar expressions, include, but are not limited to, any statements relating to our growth strategy and product development programs, including the timing of and our ability to conduct IND-enabling studies, make regulatory filings such as INDs, statements concerning the potential of therapies and product candidates, statements concerning the timing of data presentations and publications, and any other statements that are not historical facts. Forward looking statements are based on management’s current expectations and are subject to risks and uncertainties that could negatively affect our business, operating results, financial condition, and stock value. Factors that could cause actual results to differ materially from those currently anticipated include: risks relating to our growth strategy; our ability to obtain, perform under, and maintain financing and strategic agreements and relationships; risks relating to the results of research and development activities; risks relating to the timing of starting and completing clinical trials; uncertainties relating to preclinical and clinical testing; our dependence on third party suppliers; our ability to attract, integrate and retain key personnel; the early stage of products under development; our need for substantial additional funds; government regulation; patent and intellectual property matters; competition; as well as other risks described in ​“Risk Factors,” in our most recent Form 10-K and our most recent 10-Qs on file with the Securities and Exchange Commission. We expressly disclaim any obligation or undertaking to release publicly any updates or revisions to any forward-looking statements contained herein to reflect any change in our expectations or any changes in events, conditions or circumstances on which any such statement is based, except as required by law, and we claim the protection of the safe harbor for forward-looking statements contained in the Private Securities Litigation Reform Act of 1995. Investor Contact:Simon Harnest - CIO, SVP Investor Relationssimon@​metagenomi.​co Media Contact:Ashlye Hodge - Communications Managerashlye@​metagenomi.​co

Ad Hoc Announcement Pursuant to Art. 53 LR Geneva, Switzerland, August 27, 2024 - Addex Therapeutics (SIX/NASDAQ: ADXN), a clinical-stage biopharmaceutical company focused on developing a portfolio of novel small molecule allosteric modulators for neurological disorders, and Indivior PLC (NASDAQ/LSE: INDV) today announced the selection of clinical candidates from their GABAB positive allosteric modulator (PAM) research collaboration. Indivior has selected a compound for future development in substance use disorder and will now undertake all future development of their selected compound. Under the terms of the agreement, Addex is eligible for payment of up to USD 330 million on successful achievement of prespecified regulatory, clinical and commercial milestones as well as tiered royalties on the level of net sales from high single digits up to low double-digit. Under the terms of the agreement, Addex has also exercised its right to select a compound to advance its own independent GABAB PAM program for the treatment of chronic cough. "Indivior’s collaboration with Addex has been instrumental in identifying a possible candidate for the treatment of substance use disorders,” said Christian Heidbreder, Chief Scientific Officer at Indivior. “While the challenges of this field are complex, targeting the GABAB receptor with positive allosteric modulators offers a potential new avenue for developing much needed therapies. At Indivior, we are committed to advancing the science of addiction treatment, with the goal of bringing effective therapies to those affected by substance use disorders.” “The selection of GABAB PAM clinical candidates is the culmination of more than five years of research at Addex in close collaboration with the team at Indivior. During this time, we were able to pinpoint specific candidates from thousands of compounds using the power of our industrial-scale allosteric modulator discovery platform. We look forward to the next steps in the development of the substance use disorder program under the control of Indivior,” said Tim Dyer, CEO of Addex. “On the Addex side, we are now focused on advancing our selected clinical candidate for chronic cough into IND enabling studies.” About GABAB Activation with PAM: Activation of gamma-aminobutyric acid subtype B (GABAB) receptor, a Family C class of GPCR, is clinically and commercially validated. The generic GABAB receptor agonist, baclofen, marketed for spasticity, has been shown to be efficacious in several other disease areas, including alcohol use disorder, CMT1A, overactive bladder, chronic cough and pain. However, its wider use is limited due to a variety of side effects, rapid clearance and the development of tolerance. Novel, potent, selective and orally available PAMs that potentiate GABA responses, rather than acting as orthosteric agonists at the GABAB receptor, like baclofen, are expected to deliver efficacy and have fewer adverse effects. Furthermore, PAMs only act when the natural ligand (GABA) activates the receptor, hence respecting the physiological cycle of activation, which may explain why PAMs lead to less tolerance than direct agonists. About Addex:Addex Therapeutics is a clinical-stage biopharmaceutical company focused on developing a portfolio of novel small molecule allosteric modulators for neurological disorders. Addex lead drug candidate, dipraglurant (mGlu5 negative allosteric modulator or NAM), is under evaluation for future development in brain injury recovery including post-stroke and traumatic brain injury recovery. Addex partner, Indivior, has selected a GABAB PAM drug candidate for development in substance use disorders and expects to start IND enabling studies in H1 2025. Addex is advancing an independent GABAB PAM program for chronic cough and expect to start IND enabling studies in 2025. Addex is also holding a 20% equity interest in a private company, Neurosterix LLC which is advancing a portfolio of allosteric modulator programs including M4 PAM for schizophrenia, mGlu7 NAM for mood disorders and mGlu2 NAM for mild neurocognitive disorders. Addex shares are listed on the SIX Swiss Exchange and American Depositary Shares representing its shares are listed on the NASDAQ Capital Market, and trade under the ticker symbol “ADXN” on each exchange. For more information, visit www.addextherapeutics.com Contacts: Tim DyerChief Executive OfficerTelephone: +41 22 884 15 55PR@addextherapeutics.comMike SinclairPartner, Halsin Partners+44 (0)20 7318 2955msinclair@halsin.com Addex Forward Looking Statements:This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including statements about the intended use of proceeds of the offering. The words “may,” “will,” “could,” “would,” “should,” “expect,” “plan,” “anticipate,” “intend,” “believe,” “estimate,” “predict,” “project,” “potential,” “continue,” “target” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Any forward-looking statements in this press release, are based on management's current expectations and beliefs and are subject to a number of risks, uncertainties and important factors that may cause actual events or results to differ materially from those expressed or implied by any forward-looking statements contained in this press release, including, without limitation, uncertainties related to market conditions. These and other risks and uncertainties are described in greater detail in the section entitled “Risk Factors” in Addex Therapeutics’ Annual Report on Form 20-F for the year ended December 31, 2023, as filed with the SEC on April 18, 2024, the final prospectus supplement and accompanying prospectus and other filings that Addex Therapeutics may make with the SEC in the future. Any forward-looking statements contained in this press release represent Addex Therapeutics’ views only as of the date hereof and should not be relied upon as representing its views as of any subsequent date. Addex Therapeutics explicitly disclaims any obligation to update any forward-looking statements.

SEOUL, South Korea--(BUSINESS WIRE)-- ENCell Co., Ltd., a biotech in South Korea specializing in Cell and Gene therapy (CGT), presented promising results from their First-in-Human Phase 1 clinical trial of the novel mesenchymal stem cell therapy (EN001) for Charcot-Marie-Tooth disease type 1A (CMT1A) at the Peripheral Nerve Society (PNS) annual meeting in Montreal on June 23, 2024. This annual conference is a key gathering for experts in the field, including neurologists, neurosurgeons, neuroscientists, and other healthcare professionals focused on peripheral nerve disorders. EN001 is a next-generation allogeneic mesenchymal stem cell therapy developed using ENCell's proprietary ENCell Technology. ENCell reported EN001 can migrate to and regenerate damaged nerves and muscles through non-clinical studies. In June 2023, ENCell completed a Phase 1 clinical trial with nine CMT1A patients at Samsung Medical Center (SMC) with Professor Byung-Ok Choi from the Department of Neurology as the Principal Investigator. The trial utilized a dose-escalation design to ensure the safety and exploratory efficacy of EN001 over a 16-week period. The trial results, which were selected for oral presentation at the PNS meeting, showed no dose-limiting toxicity, serious adverse events, or infusion-related responses among participants, thereby confirming the safety of EN001. Additionally, exploratory efficacy evaluations revealed significant improvements. The Charcot-Marie-Tooth Neuropathy Score version 2 decreased by an average of 2.89 points (p=0.0039) after 16 weeks, with the high-dose group showing a more pronounced reduction of 3.50 points (p=0.0313). Further analysis indicated that patients receiving the high dose experienced clinical improvements in disease severity, with some moving from severe to moderate or from moderate to mild categories. Specific sensory and motor function tests also showed marked improvements, with the high-dose group. Enhancements in the 10 Meter Walking Test, Functional Disability Scale, Overall Neuropathy Limitation Score leg scale, and nerve conduction studies were also observed. An ENCell spokesperson highlighted the significance of presenting these promising clinical results at a prestigious conference, emphasizing the company's dedication to developing new treatment options for CMT patients, who currently lack approved therapies. Professor Byung-Ok Choi, leading the clinical trial, expressed optimism, stating, "These results provide hope to CMT1A patients, a group affected by a rare disease without existing treatments." ENCell is planning to conduct repeat-administration clinical trial at SMC.